Alzheimer's disease (AD) is characterized neuropathologically by an abundance of neuritic plaques and neurofibrillary tangles in areas of the brain important for cognition. AD is currently a major health problem that imposes a severe economic burden; short of an effective treatment(s) it is projected to become a dominant source of health care expenditures over the next 3 decades. Unfortunately, existing treatments are palliative and provide only temporary symptomatic benefit. Potential disease-modifying therapeutic approaches for AD have and are being tested, however, none impact disease progression.
In AD, neuritic plaques are composed predominantly of Aβ42 (8) and the most common biochemical phenotype of the more than 200 different familial AD or FAD-linked mutations is an increased ratio of Aβ42/Aβ40 (9). An important therapeutic goal for treating AD should be not just to treat AD but to prevent it. Accordingly, there is a need in the art for therapies for neuropathologies associated with Aβ peptides. Provided herein are solutions to these and other problems in the art